Genetic control of differential acetylation in diabetic rats.
Post-translational protein modifications such as acetylation have significant regulatory roles in metabolic processes, but their relationship to both variation in gene expression and DNA sequence is unclear. We address this question in the Goto-Kakizaki (GK) rat inbred strain, a model of polygenic t...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0094555 |
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| author | Pamela J Kaisaki Georg W Otto Joanna F McGouran Amine Toubal Karène Argoud Helen Waller-Evans Clare Finlay Sophie Caldérari Marie-Thérèse Bihoreau Benedikt M Kessler Dominique Gauguier Richard Mott |
| author_facet | Pamela J Kaisaki Georg W Otto Joanna F McGouran Amine Toubal Karène Argoud Helen Waller-Evans Clare Finlay Sophie Caldérari Marie-Thérèse Bihoreau Benedikt M Kessler Dominique Gauguier Richard Mott |
| author_sort | Pamela J Kaisaki |
| collection | DOAJ |
| description | Post-translational protein modifications such as acetylation have significant regulatory roles in metabolic processes, but their relationship to both variation in gene expression and DNA sequence is unclear. We address this question in the Goto-Kakizaki (GK) rat inbred strain, a model of polygenic type 2 diabetes. Expression of the NAD-dependent deacetylase Sirtuin-3 is down-regulated in GK rats compared to normoglycemic Brown Norway (BN) rats. We show first that a promoter SNP causes down-regulation of Sirtuin-3 expression in GK rats. We then use mass-spectrometry to identify proteome-wide differential lysine acetylation of putative Sirtuin-3 protein targets in livers of GK and BN rats. These include many proteins in pathways connected to diabetes and metabolic syndrome. We finally sequence GK and BN liver transcriptomes and find that mRNA expression of these targets does not differ significantly between GK and BN rats, in contrast to other components of the same pathways. We conclude that physiological differences between GK and BN rats are mediated by a combination of differential protein acetylation and gene transcription and that genetic variation can modulate acetylation independently of expression. |
| format | Article |
| id | doaj-art-df135f88f9f649eaad9b62bf58e4c475 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-df135f88f9f649eaad9b62bf58e4c4752025-08-20T03:46:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9455510.1371/journal.pone.0094555Genetic control of differential acetylation in diabetic rats.Pamela J KaisakiGeorg W OttoJoanna F McGouranAmine ToubalKarène ArgoudHelen Waller-EvansClare FinlaySophie CaldérariMarie-Thérèse BihoreauBenedikt M KesslerDominique GauguierRichard MottPost-translational protein modifications such as acetylation have significant regulatory roles in metabolic processes, but their relationship to both variation in gene expression and DNA sequence is unclear. We address this question in the Goto-Kakizaki (GK) rat inbred strain, a model of polygenic type 2 diabetes. Expression of the NAD-dependent deacetylase Sirtuin-3 is down-regulated in GK rats compared to normoglycemic Brown Norway (BN) rats. We show first that a promoter SNP causes down-regulation of Sirtuin-3 expression in GK rats. We then use mass-spectrometry to identify proteome-wide differential lysine acetylation of putative Sirtuin-3 protein targets in livers of GK and BN rats. These include many proteins in pathways connected to diabetes and metabolic syndrome. We finally sequence GK and BN liver transcriptomes and find that mRNA expression of these targets does not differ significantly between GK and BN rats, in contrast to other components of the same pathways. We conclude that physiological differences between GK and BN rats are mediated by a combination of differential protein acetylation and gene transcription and that genetic variation can modulate acetylation independently of expression.https://doi.org/10.1371/journal.pone.0094555 |
| spellingShingle | Pamela J Kaisaki Georg W Otto Joanna F McGouran Amine Toubal Karène Argoud Helen Waller-Evans Clare Finlay Sophie Caldérari Marie-Thérèse Bihoreau Benedikt M Kessler Dominique Gauguier Richard Mott Genetic control of differential acetylation in diabetic rats. PLoS ONE |
| title | Genetic control of differential acetylation in diabetic rats. |
| title_full | Genetic control of differential acetylation in diabetic rats. |
| title_fullStr | Genetic control of differential acetylation in diabetic rats. |
| title_full_unstemmed | Genetic control of differential acetylation in diabetic rats. |
| title_short | Genetic control of differential acetylation in diabetic rats. |
| title_sort | genetic control of differential acetylation in diabetic rats |
| url | https://doi.org/10.1371/journal.pone.0094555 |
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